Arthritis and musculoskeletal disorders, including temporomandibular joint disorders (TMD), are chronic pain conditions that occur more frequently in women of reproductive age than men. Current status of the neural mechanisms of articular pain has relied mainly on experimental models of the knee or ankle joint. However, organizational differences between trigeminal and spinal systems suggest the mechanisms that mediate deep craniofacial pain cannot be fully understood from results obtained by other models of joint pain. The proposed experiments use an animal model to study nociceptive signaling from the temporomandibular joint (TMJ) by neurons in the lower trigeminal brainstem under naive conditions and during chronic inflammation. The overall goal of this study is to test the hypothesis that sex steroid hormones influence central neural processing of sensory signals arising from TMJ region. Aim 1 determines if sex steroid replacement therapy (estrogen and progesterone) modifies neural activity evoked by stimulating the TMJ. Aim 2 determines if sex steroids act through glutamate receptors to modify processing of nociceptive signals from the TMJ. Aim 3 determines if mitogen-activated protein (MAP) kinase, a transduction pathway shared by estrogen and nerve growth factor, contributes to processing of nociceptive signals from the TMJ. Three approaches are used to provide converging lines of evidence: c-fos immunocytochemistry determines neural population responses at single cell resolution, microdialysis determines amino acid transmitter release and electrophysiological recording determines the properties of individual trigeminal neurons that encode sensory input from the TMJ region. This information may lead to a better understanding of how the brain integrates pain-like signals relevant for TMD in women